The Aedes aegypti L. mosquito is considered the most important vector of arboviruses in the world. Insecticide-resistant phenomenon is a difficult barrier to overcome for government health entities around the planet. This problem forces to increase the concentrations of insecticides in the environment causing environmental pollution and health threat to human beings. Plants have been used to combat pests for centuries and are an eco-friendly source for the search for molecules with larvicidal activity. In this work, 65 ethanol-soluble extracts from 56 plants of the Colombian Caribbean region were evaluated as potential larvicides against Aedes aegypti mosquito, as well as, for their toxic effects on non-target organism. A high larvicidal activity was found for 16 ethanol extracts, however, the most potent activity against the larvae was obtained for the five plant extracts corresponding to the seeds of Annona squamosa L., Annona cherimolia L., Annona muricata L., Tabernaemontana cymosa Jacq. and Mammea americana L., with LC50 value of 58.44, 65.10, 84.92, 25.02 and 38.58 ppm, respectively. T. cymosa seeds extract was selected for bio-guided fractionation due to the high larvicidal activity showed. Through chromatographic techniques and Nuclear Magnetic Resonance (NMR), five indole alkaloids were isolated and characterized from T. cymosa active fraction; among them, voacangine showed activity with a LC50 of 5.13 ppm indicating a high larvicidal potency besides low toxicity against model organism Caenorhabditis elegans. We also report a new indole alkaloid from T. cymosa. Our study demonstrated the potential of the Colombian Caribbean flora as a host of bioactive plants against important vectors such as the A. aegypti mosquito with potential use in controlled environments. © 2022 The Author(s)